Flavin-containing mono-oxygenase

Fig. 7.4.2 The origin and metabolism of TMA in man. This figure shows the molecular defect in the flavin-containing mono-oxygenase ( ) in trimethylaminuria or fish odour syndrome. The dashed line indicates the minor metabolic pathway in healthy volunteers. Enzyme steps marked with B are in the intestinal bacterial flora. DMA Dimethylamine, MMA monomethyl-...

C.T. Dolphin, A. Janmohamed, R.L. Smith, E.A. Shephard, I.R. Phillips, Missense Mutation in Flavin-containing Mono-oxygenase 3 Gene, FM03, Underlies Fish-odour Syndrome , Nat. Genet., 17, 491-494 (1997). 

Based on inhibitor studies, Wallsgrove and co-workers had been confident that at least in B. napus, flavin-containing mono-oxygenases are involved in the aldoxime formation (Bennett et al, 1993, 1995a,b Dawson et al, 1993). 

In addition to cytochrome P450s, hepatic microsomes contain another class of mono-oxygenases, the flavin-containing mono-oxygenases (FMO). These enzymes catalyse oxidation at nucleophilic nitrogen, sulfur and phosphorus atoms rather than oxidation at carbon atoms, e.g. for phenothiazines, ephedrine, norcocaine and the mono-ether and carbamate-containing pesticides. 

Ripp SE, Overby EIT, Phllpot RM, Elfarra AA. Oxidation of cysteine S-conjugates by rabbit liver microsomes and cDNA-expressed flavin-containing mono-oxygenases studies with S-(l,2-dichlorovinyl)-E-cysteine, S-(l,2,2 trichlorovinyl)-Ecysteine, S-allyl-E-cysteine, and S-benzyl-L-cysteine. Mol Pharmacol 1997 51 507-515. 

Dolphin, C. T., Janmohamed, A., Smith, R. L. et al. (1997) Missense mutation in flavin-containing mono-oxygenase 3 gene, FM03, underlies fish-odour syndrome. Nat Genet 17, 491-494. 

Basarab, T., Ashton, G. H., Menage, H. R et al. (1999) Sequence variations in the flavin-containing mono-oxygenase 3 gene (FM03) in fish odour syndrome. Br J Dermatol 140, 164-167. 

Fig. 19.13. Cytochrome P450 mono-oxygenases. Electrons are donated by NADPH to O2 and the substrate. The flavin coenzymes FAD and FMN in one subunit transfer single electrons to cytochrome P450, which is an Fe-heme containing protein that absorbs hght at a wavelength of 450 nm. The enzyme is embedded in a membrane, usually the endoplasmic reticulum.

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